Erythrocyte Count and the Human Natural Lifespan Limit: Evidence from the Long Life Family Study

Arbeev, K. G.; Bagley, O.; Murabito, J. M.; Cohen, H. J.; Pierce, B. L.; Johnson, W. E.; Eisenberg, D. T. A.; Mahajan, M. C.; Andersen, S. L.; Christensen, K.; Zmuda, J. M.; Thyagarajan, B.; Luo, S.; Yashin, A. I.; Province, M. A.; Aviv, A.

doi:10.64898/2026.06.08.730977

bioRxiv · 10.64898/2026.06.08.730977

Erythrocyte Count and the Human Natural Lifespan Limit: Evidence from the Long Life Family Study

Arbeev, K. G.·Bagley, O.·Murabito, J. M.·Cohen, H. J.·Pierce, B. L.·Johnson, W. E.·Eisenberg, D. T. A.·Mahajan, M. C.·Andersen, S. L.·Christensen, K.·Zmuda, J. M.·Thyagarajan, B.·Luo, S.·Yashin, A. I.·Province, M. A.·Aviv, A.

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Abstract

Erythropoiesis is the most replication-intensive process in the body. Its lifelong replicative demands may erode hematopoietic cells replicative capacity, leading to a decline in erythrocyte count (EC) in older adults and limiting their lifespan. We examined the relationship between EC and mortality among 1,620 participants aged [≥]70 years in the Long Life Family Study and found that lower EC further augmented the exponential, age-dependent rise in mortality. We identified an EC threshold (ECT) (3.8x1012/L) below which mortality was amplified (p=9.3x10-6). As EC declined with age (p=8.2x10-18), it fell below this threshold in many participants, sharply increasing their mortality risk. This mortality-based ECT emerged from modeling, independent of the World Health Organization anemia definition, which is based on statistical thresholds (5th centiles) of hemoglobin distribution in populations [≤] 65 years. Thus, declining EC may be one of the biological factors imposing a natural lifespan limit on many older adults.

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Arbeev, K. G., Bagley, O., Murabito, J. M., Cohen, H. J., Pierce, B. L., Johnson, W. E., Eisenberg, D. T. A., Mahajan, M. C., Andersen, S. L., Christensen, K., Zmuda, J. M., Thyagarajan, B., Luo, S., Yashin, A. I., Province, M. A., Aviv, A.. 2026-06-15. Erythrocyte Count and the Human Natural Lifespan Limit: Evidence from the Long Life Family Study. https://doi.org/10.64898/2026.06.08.730977

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